Nutrition and aberrant DNA methylation patterns in atherosclerosis: more than just hyperhomocysteinemia?

Abstract

Methylation is a reversible modification of DNA participating in epigenetic regulation of gene expression. It is now clear that atherosclerosis is associated with aberrant DNA methylation patterns in the vascular tissue and peripheral blood cells, but the origin of this anomaly is poorly understood. Based on evidence that global DNA hypomethylation coexists with hyperhomocysteinemia in advanced human atherosclerosis, it is widely assumed that altered DNA methylation patterns in atherosclerosis are mainly secondary to a decrease in factors essential for the synthesis of S-adenosyl methionine (SAM, the main methyl group donor in DNA methylation reactions), such as folate and vitamin B-12, or to homocysteine-induced blocking of SAM biosynthesis. Nonetheless, recent work expanded this view by showing that both local DNA hyper- and hypomethylation occur in early atherosclerosis in normohomocysteinemic mice and that atherogenic lipoprotein profiles promote DNA hypermethylation in cultured human macrophages. These findings suggest that during early atherosclerosis, nutritional factors affect DNA methylation patterns by mechanisms that are likely to be independent of vitamin or homocysteine levels. These data have the potential to assist in the identification of preventive or therapeutic avenues for cardiovascular disease.